Project Summary/Abstract: Heterosexual transmission is now the predominant source of new HIV infections and the number of infections in women is on the rise. Lack of knowledge about risk factors in postmenopausal women that can increase their susceptibility to HIV is becoming a major issue as many women continue to be sexually active beyond menopause. Although it is known that aging results in loss of sex hormones and reduction of certain immune functions, there remains a major gap in our understanding regarding the loss of innate immune functions in the female reproductive tract following menopause, particularly in the context of HIV acquisition and transmission. An additional critical co-factor that might exacerbate HIV susceptibility in older women is sexual trauma, which is severely under-reported. Postmenopausal women are more prone to vaginal injury and infections following sexual violence due to the thinning and dryness of vaginal mucosa and slower wound healing processes. Our goal in this proposal is to test the hypothesis that the loss of sex hormones at menopause, compromise immune protection in the female reproductive tract. We will evaluate loss of immune protection in the context of pathogen recognition and response, regulation by sex hormones, as well as the influence of mucosal injury resulting from sexual violence. We hypothesize that all these parameters will impact HIV susceptibility in aging women. This study will provide us with a unique outlook on susceptibility of postmenopausal women to sexually transmitted HIV and examine immune alterations following mucosal injuries resulting from sexual violence. This is significant because our findings can be used to promote the development of prevention/intervention strategies specifically designed to boost genital tract immunity in older women.